- Proton and Cu(II) binding to tren-based tris-macrocycles. Affinity towards nucleic acids and nuclease activity
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Proton binding by the two tren-based tris-macrocycles L1 and L2, composed, respectively, by three 1,4,7,10-tetrazacyclododecane ([12]aneN4) and three 1-oxa-4,7,10-triazacyclododecane ([12]aneN3O) macrocyclic moieties appended to a "tren" unit (tren = tris(2-aminoethyl)amine), has been analyzed by means of potentiometric and 1H and 13C NMR measurements in aqueous solutions. This study reveals that the ligands form highly charged polyammonium cations at neutral pH, containing six acidic protons equally distributed among the three macrocyclic units. A potentiometric and UV-vis spectrophotometric study shows that both ligands can form stable trinuclear Cu(II) complexes in a wide pH range. In the polynuclear complexes each metal is coordinated to a single macrocyclic unit. While the Cu(II) complexes with L1 do not show any tendency to form hydroxylated complexes, the mono-, di- and trinuclear L2 complexes give stable hydroxo-complexes, present in aqueous solutions from slightly acidic to alkaline pH values. Melting point studies indicate that the new tris-macrocyles and their Cu(II) complexes lead to stronger stabilization of double-stranded nucleic acids than those observed earlier with analogous ditopic macrocyclic ligands, again with preference for RNA-type polymers compared to DNA. The copper complexes promote cleavage of plasmid DNA and of bis-p-nitrophenyl phosphate (BNPP). Particular rate enhancements for BNPP with some complexes are attributed to the simultaneous action of three metal ions and partially to the formation of hydroxo complexes at neutral pH. The Royal Society of Chemistry 2003.
- Bencini, Andrea,Berni, Emanuela,Biancini, Antonio,Giorgi, Claudia,Valtancoli, Barbara,Chand, Dillip Kumar,Schneider, Hans-Joerg
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- Effect of hydrophobic interaction cooperating with double Lewis acid activation in a zinc(ii) phosphodiesterase mimic
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The novel dinuclear Zn(ii) complex (1) containing a β-CD dimer could accelerate BNPP (a DNA substitute) hydrolysis more efficiently than catalyze HPNP (a RNA substitute) transesterification with different mechanisms involved; the β-CDs played remarkably different roles.
- Zhao, Meng,Zhang, Li,Chen, Huo-Yan,Wang, Han-Lu,Ji, Liang-Nian,Mao, Zong-Wan
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Read Online
- An insight into phosphorylase mechanism from model study
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Mechanistic aspects of phosphorylation reaction that mimic phosphorylase enzymes have been studied in the biologically important middle pH region by utilizing nitrophenol as substrate and bistrimethylenediaminecobalt(III) phosphate complexes as the enzyme model. Significant phosphorylation was noted from reactions of 1:1 molar ratio of nitrophenol and bistrimethylenediamincobalt(III) phosphate, [Co(III)tn2Pi]. Enhanced phosphorylation was depicted for reaction solutions that contained 1:1 molar ratio of nitrophenol and di-bistrimethylenediamincobalt(III) phosphate, [(Co(III)tn2)2Pi]. Specific mechanistic features and the possible roles metal ions play in phosphorylase enzyme are highlighted. Copyright Taylor & Francis Group, LLC.
- Tafesse, Fikru,Eguzozie, Kennedy
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- Rapid phosphodiester hydrolysis by an ammonium-functionalized copper(II) complex. A model for the cooperativity of metal ions and NH-acidic groups in phosphoryl transfer enzymes
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The copper(II) complexes (L(n))Cu(NO3)4·2(H2O)] (n = 1: 1, n = 2: 2) of the ammonium-functionalized ligands [6,6'-(Me2HNCH2C≡-C)2bpy]2+ (L1) and [6,6'-(Me3NCH2C≡C)2 bpy]2+ L2 were prepared. Hydrolysis of the activated phosphodiester bis(p-nitrophenyl) phosphate (BNPP) by these complexes in ethanol-water 19:1 at 20°C was investigated. The rate constants for cleavage of the bound phosphodiester at pH 6.6 are k(cat) = 4.4(±0.4) x 10-3 s-1 for (L1)Cu and k(cat) = 4(±1) x 10-6 s-1 for (L1)Cu. (L1)CU accelerates hydrolysis of BNPP 4 x 107-fold and is 1000 times more reactive than (L2)Cu. This suggests that the high reactivity of (L1)CU is related to the interaction of the acidic -NMe2H+ group with the phosphodiester substrate. Bifunctional binding of a phosphate ester by metal coordination and hydrogen bonding with one ammonium group is observed in the crystallographically characterized complex [(L1)2Cu2(1,3-μ-O3POPh)2(OH2)2](NO3)4 (3). A plausible mechanism of BNPP cleavage by (L1)CU includes metal-hydroxide attack to the phosphodiester which is doubly activated by coordinative and hydrogen bonding. The copper(II) complex of L1 represents a simple model for the efficient cooperativity of metal ions and NH-acidic amino acid side chains (Lys-ammonium, Arg-guanidinium, His-imidazolium) in enzymes that catalyze the cleavage of phosphate di- and monoesters.
- K?vári, Endre,Kr?mer, Roland
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- Catalytic zinc complexes for phosphate diester hydrolysis
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Creating efficient artificial catalysts that can compete with biocatalysis has been an enduring challenge which has yet to be met. Reported herein is the synthesis and characterization of a series of zinc complexes designed to catalyze the hydrolysis of phosphate diesters. By introducing a hydrated aldehyde into the ligand we achieve turnover for DNA-like substrates which, combined with ligand methylation, increases reactivity by two orders of magnitude. In contrast to current orthodoxy and mechanistic explanations, we propose a mechanism where the nucleophile is not coordinated to the metal ion, but involves a tautomer with a more effective Lewis acid and more reactive nucleophile. This data suggests a new strategy for creating more efficient metal ion based catalysts, and highlights a possible mode of action for metalloenzymes.
- Tirel, Emmanuel Y.,Bellamy, Zoe,Adams, Harry,Lebrun, Vincent,Duarte, Fernanda,Williams, Nicholas H.
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- P-nitrophenyl phosphate disodium and preparation method thereof
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The invention provides p-nitrophenyl phosphate disodium and a preparation method thereof. The preparation method comprises the following steps: 1, enabling p-nitrophenol to react with dialkyl chloridephosphate in the presence of an alkali so as to obtain O,O-dialkyl p-nitrophenyl phosphate; 2, performing an alkyl ester desorption reaction on the O,O-dialkyl p-nitrophenyl phosphate and a compoundwith trimethylsilyl groups so as to obtain O,O-di(trimethylsilyl) p-nitrophenyl phosphate; 3, performing a hydrolysis reaction on the O,O-di(trimethylsilyl) p-nitrophenyl phosphate so as to obtain p-nitrophenyl phosphate; and 4, enabling the p-nitrophenyl phosphate to react with sodium hydroxide, so as to obtain the p-nitrophenyl phosphate disodium. According to the preparation method provided bythe invention, the intermediate product obtained in the step 1 can be purified through vacuum distillation, and byproducts which are hard to remove are not generated in later operation of ether hydrolysis or pH value adjustment, so that the purification difficulty of the product is greatly reduced; and due to selection of the compound with the trimethylsilyl groups, hydrolysis can be implemented thoroughly, and in addition, the system can be clean.
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- Carbonate-bridged dinuclear lanthanide(III) complexes of chiral macrocycle
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Mononuclear Eu(III) and Dy(III) complexes of the chiral hexaaza macrocycle L, 2(R),7(R),18(R),23(R)-1,8,15,17,24,31-hexaazatricyclo[25.3.1.1.0.0]-dotriaconta-10,12,14,26,28,30-hexaene have been obtained as chloride derivatives (1 and 2, respectively) and
- Gerus, Aleksandra,?lepokura, Katarzyna,Lisowski, Jerzy
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supporting information
p. 115 - 121
(2019/06/11)
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- Transition States and Control of Substrate Preference in the Promiscuous Phosphatase PP1
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Catalytically promiscuous enzymes are an attractive frontier for biochemistry, because enzyme promiscuities not only plausibly explain enzyme evolution through the mechanism of gene duplication but also could provide an efficient route to changing the catalytic function of proteins by mimicking this evolutionary process. PP1γ is an effectively promiscuous phosphatase for the hydrolysis of both monoanionic and dianionic phosphate ester-based substrates. In addition to its native phosphate monoester substrate, PP1γ catalyzes the hydrolysis of aryl methylphosphonates, fluorophosphate esters, phosphorothioate esters, and phosphodiesters, with second-order rate accelerations that fall within the narrow range of 1011-1013. In contrast to the different transition states in the uncatalyzed hydrolysis reactions of these substrates, PP1γ catalyzes their hydrolysis through similar transition states. PP1γ does not catalyze the hydrolysis of a sulfate ester, which is unexpected. The PP1γ active site is tolerant of variations in the geometry of bound ligands, which permit the effective catalysis even of substrates whose steric requirements may result in perturbations to the positioning of the transferring group, both in the initial enzyme-substrate complex and in the transition state. The conservative mutation of arginine 221 to lysine results in a mutant that is a more effective catalyst toward monoanionic substrates. The surprising conversion of substrate preference lends support to the notion that mutations following gene duplication can result in an altered enzyme with different catalytic capabilities and preferences and may provide a pathway for the evolution of new enzymes.
- Chu, Yuan,Williams, Nicholas H.,Hengge, Alvan C.
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p. 3923 - 3933
(2017/08/07)
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- Characterization of wall teichoic acid degradation by the bacteriophage φ29 appendage protein GP12 using synthetic substrate analogs
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Background: The GP12 protein from bacteriophage φ29 is a likely wall teichoic acid hydrolase. Results: GP12 is an efficient catalyst of wall teichoic acid hydrolysis that is influenced by glycosylation of the wall teichioc acid polymer. Conclusion: GP12 m
- Myers, Cullen L.,Ireland, Ronald G.,Garrett, Teresa A.,Brown, Eric D.
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p. 19133 - 19145
(2015/09/08)
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- Synthesis, structure, DNA interaction, and hydrolytic function toward bis(p-nitrophenyl) phosphate of a heterobinuclear macrocyclic complex
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An asymmetrical bis-pyridine pendant-armed macrocyclic heterobinuclear complex, [ZnNiL](ClO4)2?CH3CN (H 2L was derived from the condensation between 3,3′-((ethane-1,2- diylbis((pyridin-2-ylmethyl)azanediyl))bis(methylene))bis(2-hydroxy-5- methylbenzaldehyde) and 1.3-diaminopropane), has been synthesized and characterized by physico-chemical and spectroscopic methods. The asymmetric unit contains two complete macrocyclic complexes that are nevertheless quite similar to one another. The Zn-Ni separations, bridged by the two phenoxides, are 3.107 and 3.141 A, respectively. The phosphate hydrolysis catalyzed by the complex was investigated using bis(4-nitrophenyl)phosphate (BNPP) as the substrate. The catalytic rate constant (k cat) is 1.64 × 10-3 s-1 at pH 7.4 and 25 °C, which is 10 8-fold higher than that of the corresponding uncatalyzed reaction. The interaction between the complex and calf thymus (CT) DNA was investigated by UV-vis absorption, viscosity experiments, and cyclic voltammetry. The complex shows good binding propensity to calf thymus DNA via intercalation with a binding constant of 5 × 104 M-1. The agarose gel electrophoresis studies show that the complex has a concentration-dependent DNA cleavage activity.
- Mao, Jia Wei,Zhou, Hong,Chen, Yun Feng,Cheng, Gong Zhen,Pan, Zhi Quan
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experimental part
p. 385 - 391
(2012/09/08)
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- Binuclear copper(II) complexes 1: Synthesis, characterization and evaluation of a new complex in phosphatase-like activity
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A new binuclear Cu(II) complex derived from a pamoic type ligand has been synthesized and characterized by X-ray crystallography. This complex was checked as catalysts in the hydrolysis of bis(p-nitrophenyl)phosphate. Its catalytic properties were studied
- Schicke, Olivier,Faure, Bruno,Giorgi, Michel,Simaan, A. Jalila,Réglier, Marius
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experimental part
p. 189 - 194
(2012/10/08)
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- Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate δ-ester modifications as selective agonists of the P2Y4 receptor
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P2Y2 and P2Y4 receptors are G protein-coupled receptors, activated by UTP and dinucleoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5′-triphosphates and 5′-tetraphosphate esters. P2Y4 receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N4-alkyloxycytidine derivatives. OH groups on a terminal δ-glucose phosphoester of uridine 5′-tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N4-(Phenylpropoxy)-CTP 16 (MRS4062), Up 4-[1]3′-deoxy-3′-fluoroglucose 34 (MRS2927), and N 4-(phenylethoxy)-CTP 15 exhibit ≤10-fold selectivity for human P2Y4 over P2Y2 and P2Y6 receptors (EC 50 values 23, 62, and 73 nM, respectively). δ-3-Chlorophenyl phosphoester 21 of Up4 activated P2Y2 but not P2Y 4 receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y2 and P2Y4 receptor models indicated greater steric tolerance of N4-phenylpropoxy group at P2Y4. Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y4 receptor-selective agonists.
- Maruoka, Hiroshi,Jayasekara, M. P. Suresh,Barrett, Matthew O.,Franklin, Derek A.,De Castro, Sonia,Kim, Nathaniel,Costanzi, Stefano,Harden, T. Kendall,Jacobson, Kenneth A.
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p. 4018 - 4033
(2011/08/05)
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- Ester catalytic hydrolysis by a tridentate N,N′,N″-copper bridged cyclodextrin dimer
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A new pyridine bridged cyclodextrin dimer mono-copper complex (CuL) was synthesized and characterized. The hydrolysis of carboxylic acid esters, bis(4-nitrophenyl)carbonate (BNPC) and 4-nitrophenyl acetate (NA), and phosphate ester, a DNA model bis(4-nitrophenyl)phosphate (BNPP), promoted by CuL has been investigated. The resulting hydrolysis rate constants showed that CuL had a very high rate of catalysis for BNPC hydrolysis, yielding a 2.73 × 10 3-fold rate enhancement over uncatalyzed hydrolysis at pH 7.00, compared to only a 78.2-fold rate enhancement for NA hydrolysis. The initial first-order rate constant of catalytic hydrolysis for BNPP was 1.01 × 10-7 s-1 at pH 8.5, 35 °C and 0.1 mM catalyst concentration, about 1260-fold acceleration over uncatalyzed hydrolysis. The second rate constant kBNPP of BNPP hydrolysis promoted by CuL was found to be 5.94 × 10-4 M-1 s-1.
- Tang, Si-Ping,Chen, Sha,Wu, Guang-Fei,Chen, Huo-Yan,Mao, Zong-Wan,Ji, Liang-Nian
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experimental part
p. 184 - 188
(2011/04/22)
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- Structural and catalytic performance of a polyoxometalate-based metal-organic framework having a lanthanide nanocage as a secondary building block
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A polyoxometalate-based lanthanide-organic framework was achieved using the {[Ho4(dpdo)8(H2O)16BW 12O40] (H2O)2}7+ nanocage as a secondary building block fo
- Dang, Dongbin,Bai, Yan,He, Cheng,Wang, Jian,Duan, Chunying,Niu, Jingyang
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body text
p. 1280 - 1282
(2010/04/25)
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- Ester hydrolysis by a cyclodextrin dimer catalyst with a tridentate N,N′,N″-zinc linking group
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A new β-cyclodextrin dimer, 2,6-dimethylpyridine-bridged-bis(6- monoammonio-β-cyclodextrin) (pyridyl BisCD, L), is synthesized. Its zinc complex (ZnL) is prepared, characterized, and applied as a catalyst for diester hydrolysis. The formation constant (log KML = 7.31 ±0.04) of the complex and deprotonation constant (pKa1 = 8.14 ±0.03, pKa2 = 9.24 ±0.01) of the coordinated water molecule were determined by a potentiometric pH titration at (25±0.1)°C, indicating a triden-tate N,N′',N′′-zinc coordination. Hydrolysis kinetics of carboxylic acid esters were determined with bis(4-nitrophe-nyl) carbonate (BNPC) and 4-nitro-phenyl acetate (NA) as the substrates. The resulting hydrolysis rate constants show that ZnL has a very high rate of catalysis for BNPC hydrolysis, yielding an 8.98 × 103-fold rate enhancement over uncatalyzed hydrolysis at pH 7.00, compared to only a 71.76-fold rate enhancement for NA hydrolysis. Hydrolysis kinetics of phosphate esters catalyzed by ZnL are also investigated using bis(4-nitrophenyl)phosphate (BNPP) and disodium 4-nitrophenyl phosphate (NPP) as the substrates. The initial first-order rate constant of cata- lytic hydrolysis for BNPP was 1.29 × 10-7 s-1 at pH 8.5, 35°C and 0.1 mm catalyst concentration, about 1600-fold acceleration over uncatalyzed hydrolysis. The pH dependence of the BNPP cleavage in aqueous buffer was shown as a sigmoidal curve with an inflection point around pH 8.25, which is nearly identical to the pKa value of the catalyst from the potentiometric titration. The kBNPP of BNPP hydrolysis promoted by ZnL is found to be 1.68 × 10-3 m-1 S-1, higher than that of NPP, and comparatively higher than those promoted by its other tridentate N,N′,N′′-zinc analogues.
- Tang, Si-Ping,Zhou, Ying-Hua,Chen, Huo-Yan,Zhao, Cun-Yuan,Mao, Zong-Wan,Ji, Liang-Nian
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experimental part
p. 1354 - 1360
(2010/04/23)
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- Copper(II) complexes of N-methylated derivatives of ortho- and meta-xylyl-bridged bis(1,4,7-triazacyclononane) ligands: Synthesis, X-ray structure and reactivity as artificial nucleases
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Two new binucleating ligands, 1,3-bis[(4,7-dimethyl-1,4,7-triazacyclononan- 1-yl)methyl]benzene (Lmemx) and 1,2-bis-[(4,7-dimethyl-1,4,7- triazacyclononan-1-yl)methyl]benzene (Lmeox), have been prepared from 1,4,7-triazatricyclo-[5.2
- Belousoff, Matthew J.,Graham, Bim,Spiccia, Leone
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experimental part
p. 4133 - 4139
(2009/02/07)
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- A structural and catalytic model for zinc phosphoesterases
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A structural model for the active site of phosphoesterases, enzymes that degrade organophosphate neurotoxins, has been synthesised. The ligand [2-((2-hydroxy-3-(((2-hydroxyethyl)(pyridin-2-ylmethyl)amino)methyl) -5-methylbenzyl)(pyridin-2-ylmethyl)amino)a
- Buchholz, Rebecca R.,Etienne, Morgan E.,Dorgelo, Anneke,Mirams, Ruth E.,Smith, Sarah J.,Chow, Shiao Yun,Hanton, Lyall R.,Jameson, Geoffrey B.,Schenk, Gerhard,Gahan, Lawrence R.
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experimental part
p. 6045 - 6054
(2009/02/08)
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- Ester hydrolysis by a cyclodextrin dimer catalyst with a metallophenanthroline linking group
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A novel β-cyclodextrin dimer, 1,10-phenanthroline-2,9-dimethyl- bridged-bis(6-monoammonio-β-cyclodextrin) (phenBisCD, L), was synthesized. Its zinc complex (ZnL) has been prepared, characterized, and applied as a new catalyst for diester hydrolysis. The formation constant (logK ML=9.56±0.01) of the complex and deprotonation constant (pKa = 8.18±0.04) of the coordinated water molecule were determined by a Potentiometric pH titration at (298±0.1) K. Hydrolytic kinetics of carboxylic acid esters were performed with bis(4-nitrophenyl) carbonate (BNPC) and 4-nitrophenyl acetate (NA) as substrates. The obtained hydrolysis rate constants showed that ZnL has a very high rate of catalysis for BNPC hydrolysis, giving a 3.89×104-fold rate enhancement over uncatalyzed hydrolysis at pH 7.01, relative to only a 42-fold rate enhancement for NA hydrolysis. Moreover, the hydrolysis second-order rate constants of both BNPC and NA greatly increases with pH. Hydrolytic kinetics of a phosphate diester catalyzed by ZnL was also investigated by using bis(4-nitrophenyl) phosphate (BNPP) as the substrate. The pH dependence of the BNPP cleavage in aqueous buffer shows a sigmoidal curve with an inflection point around pH 8.11, which was nearly identical to the pKa value from the Potentiometrie titration. The Kcat of BNPP hydrolysis promoted by ZnL was found to be 9.9×10-4M-1s-1, which is comparatively higher than most other reported ZnII-based systems. The possible intermediate for the hydrolysis of BNPP, BNPC, and NA catalyzed by ZnL is proposed on the basis of kinetic and thermodynamic analysis.
- Zhou, Ying-Hua,Zhao, Meng,Mao, Zong-Wan,Ji, Liang-Nian
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experimental part
p. 7193 - 7201
(2009/08/10)
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- Probing the origin of the compromised catalysis of E. coli alkaline phosphatase in its promiscuous sulfatase reaction
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The catalytic promiscuity of E. coli alkaline phosphatase (AP) and many other enzymes provides a unique opportunity to dissect the origin of enzymatic rate enhancements via a comparative approach. Here, we use kinetic isotope effects (KIEs) to explore the origin of the 109-fold greater catalytic proficiency by AP for phosphate monoester hydrolysis relative to sulfate monoester hydrolysis. The primary 18O KIEs for the leaving group oxygen atoms in the AP-catalyzed hydrolysis of p-nitrophenyl phosphate (pNPP) and p-nitrophenylsulfate (pNPS) decrease relative to the values observed for nonenzymatic hydrolysis reactions. Prior linear free energy relationship results suggest that the transition states for AP-catalyzed reactions of phosphate and sulfate esters are "loose" and indistinguishable from that in solution, suggesting that the decreased primary KIEs do not reflect a change in the nature of the transition state but rather a strong interaction of the leaving group oxygen atom with an active site Zn2+ ion. Furthermore, the primary KIEs for the two reactions are identical within error, suggesting that the differential catalysis of these reactions cannot be attributed to differential stabilization of the leaving group. In contrast, AP perturbs the KIE for the nonbridging oxygen atoms in the reaction of pNPP but not pNPS, suggesting a differential interaction with the transferred group in the transition state. These and prior results are consistent with a strong electrostatic interaction between the active site bimetallo Zn2+ cluster and one of the nonbridging oxygen atoms on the transferred group. We suggest that the lower charge density of this oxygen atom on a transferred sulfuryl group accounts for a large fraction of the decreased stabilization of the transition state for its reaction relative to phosphoryl transfer.
- Catrina, Irina,O'Brien, Patrick J.,Purcell, Jamie,Nikolic-Hughes, Ivana,Zalatan, Jesse G.,Hengge, Alvan C.,Herschlag, Daniel
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p. 5760 - 5765
(2008/02/04)
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- Mono- versus binuclear copper(II) complexes in phosphodiester hydrolysis
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Mono- and dinuclear copper(II) complexes [Cu(L1OH)]-(CF 3SO3)2 (1) and [Cu2(L 2O)](CF3SO3)3 (2) have been synthesized and characterized by X-ray crystallography. Complexes 1 and 2 were then tested as catalysts for the hydrolysis of bis(p-nitrophenyl)phosphate (BNPP). At pH 6, the dinuclear complex 2 was found to be 20-fold more active than complex 1 and the reaction up to 600-fold faster than the un-promoted reaction. On the basis of potentiometric studies, we were able to demonstrate that the bis(aqua)copper complex was the active species by the formation of a ternary complex in which one copper atom binds to a hydroxide and the second, to the substrate. We also propose that BNPP reacts with the bis(aqua)copper complex to give a stable, hydrolytically inactive BNPP-2 complex (3). Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Selmeczi, Katalin,Giorgi, Michel,Speier, Gabor,Farkas, Etelka,Reglier, Marius
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p. 1022 - 1031
(2007/10/03)
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- Transition metal complexes of n, n',n″trialkyl-cis-1,3,5-triaminocyclohexane and related compositions and methods of synthesis and use
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The present invention provides transition metal complexes of N,N′,N″-trialkyl-cis,cis-1,3,5-triaminocyclohexane and related compositions and methods of synthesis and use in vitro and in vivo, such as a therapeutic agent or a delivery/imaging agent.
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Page/Page column 9-11
(2008/06/13)
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- Small ligands interacting with the phosphotyrosine binding pocket of the Src SH2 protein
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Various small fragments bearing phosphate, phosphonate or phosphonic acid moieties have been prepared through parallel synthesis and their binding potencies evaluated on the Src SH2 protein using a BIAcore assay. This provided us insight into the requirement of the Src SH2 pTyr binding pocket and some promising small ligands have been characterised.
- Deprez, Pierre,Mandine, Eliane,Gofflo, Dominique,Meunier, Stephane,Lesuisse, Dominique
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p. 1295 - 1298
(2007/10/03)
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- Remarkable enhancement of the hydrolyses of phosphoesters by dinuclear centers: Streptomyces aminopeptidase as a 'natural model system'
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The transition-state analogues bis(p-nitrophenyl)phosphate and p-nitrophenyl phenylphosphonate for peptide hydrolysis are shown to be very effectively hydrolyzed by Streptomyces dinuclear aminopeptidase and its Co2+, Ni2+, Mn2+
- Ercan,Hyun Ik Park,Ming
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p. 2501 - 2502
(2007/10/03)
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- Divalent metal ion-catalyzed hydrolysis of phosphorothionate ester pesticides and their corresponding oxonates
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The divalent metal ion-catalyzed hydrolysis of thionate (P=S) and oxonate (P=O) organophosphorus pesticides has been examined in light of three possible catalysis mechanisms: (1) metal ion coordination of the thionate sulfur or oxonate oxygen to enhance the electrophilicity of the phosphorus electrophilic site; (2) metal ion coordination and induced deprotonation of water to create a reactive nucleophile; and (3) metal ion coordination of the leaving group to facilitate its exit. The effect of the following metals at a concentration of 1 mM was examined: Co(II), Ni(II), Cu(II), Zn(II), and Pb(II). These metal ions were chosen for their ability to complex organic ligands and inorganic nucleophiles. Of these metal ions, Cu(II) possesses properties most suitable for all three catalytic mechanisms and serves as the most effective catalyst for the five thionate esters (chlorpyrifos-methyl, zinophos, diazinon, parathion-methyl, and ronnel) and the two oxonate esters (chlorpyrifos-methyl oxon and paraoxon) included in this study. A decrease in the degree of Cu(II) catalysis at high pH arises from solubility limitations. Pb(II) nearly matches Cu(II) as a catalyst for oxonate esters, but is a less effective catalyst for thionate esters. Catalysis by Co(II), Ni(II), and Zn(II) is negligible. Phenolate product analysis indicates that metal catalysis in some instances shifts hydrolysis from alkyl carbon-centered pathways to phosphorus-centered pathways.
- Smolen, Jean M.,Stone, Alan T.
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p. 1664 - 1673
(2007/10/03)
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- Metal-Ammonium Cooperativity in Phosphodiester Hydrolysis
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The copper(II) complex of the ammonium-functionalized ligand 2+ L1 accelerates phosphodiester hydrolysis with greater efficiency compared with related complexes which do not contain such functional groups.
- Koevari, Endre,Heitker, Jutta,Kraemer, Roland
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p. 1205 - 1206
(2007/10/02)
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- Zinc(II) Complexes of the Ammonium-Functionalized 2,2'-Bipyridine 2bpy>(ClO4)2 and of the Related Ligand 6,6'-(CH3CH2CH2CC>2bpy
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The 2,2'-bipyridine derivative 6,6'-(Me2NCH2CC)2bpy (1b) was prepared by palladium-catalyzed C-C coupling reaction.Protonation of 1b with HX yielded the ammonium salts 2bpy>X2 (2a, X = NO3(-); 2b, X = ClO4(-)). 2a was characterized by
- Koevari, Endre,Kraemer, Roland
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p. 2151 - 2158
(2007/10/02)
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- Pyranine phosphate as a new fluorigenic substrate for acidic and alkaline phosphatases
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8-Hydroxypyrene-1,3,6-trisulfonic acid (HPTS, pyranine) is highly fluorescent not only in the alkaline range but also at an acidic pH, and in a water-soluble fluorescent compound. By phosphorylation of a pyranine, its fluorescence intensity was quenched markedly. A pyranine phosphate was shown to be a potential fluorogenic substrate for the assay of acid and alkaline phosphatases, and also for phosphatase activities in human serum.
- Sato,Chiba,Hoshi,Kanaoka
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p. 786 - 788
(2007/10/02)
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- Enhanced Base Hydrolysis of Coordinated Phosphate Esters: The Reactivity of an Unusual Cobalt(III) Amine Dimer
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The hydrolysis of the dimeric cation bis(μ-4-nitrophenyl phosphato)bis(2+) has been studied at pH 10 and over the hydroxide concentration range 0.05-1.0 M.Product distribution, kinetics (involving 4-nitrophenol release), and 31P NMR and 18O tracer studies were carried out to establish the course of the reaction.In a rapid first step, the eight-membered ring of the dimer is opened by rupture of one of the Co-O bonds (SN1cB) to give a cis hydroxo complex.The ring-opened species reacts further via two competing pathways: (a) intramolecular attack of the coordinated hydroxide upon the bridging phosphate ester moiety and (b) further cleavage of the dimer by base-catalyzed (SN1cB) rupture of some Co-O bonds.Route a results in ester hydrolysis with the concomitant formation of a chelated bridging phosphate species whereas route b yields cis- and trans-hydroxy(p-nitrophenyl phosphate)bis(1,2-ethanediamine)cobalt(III).The phosphate chelate ring in the initial product of path a is subsequently opened by Co-O bond rupture and the resultant dimeric bridging phosphato species slowly decomposes to cis- and trans-hydroxo(phosphato)bis(1,2-ethanediamine)cobalt(III).Comparison of the rate data for hydrolysis of the dimer and the cis-hydroxo(4-nitrophenyl phosphato)bis(1,2-ethanediamine)cobalt(III) ion indicates that the attack by the intramolecular nucleophile is largely responsible for the enhanced rate of ester hydrolysis (ca 1E5) with a smaller contribution from charge neutralization at the P center by the metal ion (ca 10-100).Parallel kinetic studies on the analogous dimer bis(μ-4-nitrophenyl phosphato)bis(2+), previously incorrectly formulated as a monomeric species containing chelated phosphate ester, indicate that ester hydrolysis in this complex proceeds by a similar mechanism to that for the 1,2-ethanediamine complex.In total, the results are rationalized in relation to a possible mechanism for the Zn2+ containing enzyme E. coli alkaline phosphatase.
- Jones, David R.,Lindoy, Leonard F.,Sargeson, Alan M.
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p. 7807 - 7819
(2007/10/02)
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- O-Alkyl p,p'-Dianisyl Phosphinite - A New Phosphorylating Reagent
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Phosphorylation of alcohols and phosphates forming mixed esters of phosphoric acid and symmetrical pyrophosphates through O-alkyl p,p'-dianisyl phosphinite in the presence of 2,2'-dipyridyl disulphide has been investigated.
- Agrawal, Sudhir,Misra, Krishna
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p. 513 - 515
(2007/10/02)
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